The proposed studies will explore the physiological relevance and mechanism(s) of action of the putative endogenous satiety agent, human satietin (h-SAT). SAT is unlike other known satiety compounds in that it produces a long-term suppression of body weight (BW) that continues when food intake (Fl) has returned to normal. In these studies a purer form of h-SAT (ph-SAT) will be utilized than used previously. It will be determined what portion of the previously observed Fl and BW suppression following intracerebroventricular (ICV) infusion of SAT was due to contaminants and what can be attributed to ph-SAT. Next, a dose response curve of ICV infused ph-SAT will be established to gain insight on its specificity. The specificity of ph-SAT will be further explored using a two-bottle taste test, place aversion test, and meal pattern analyses. It will be determined whether ph-SAT suppresses Fl and BW directly or through changes in blood metabolites and selected hormones, alternately, it will be established if ph-SAT non-specifically be measuring certain plasma enzymes and doing a WBC. It will be determined whether repeated ICV and i.p. infusions of ph-SAT can continually suppress Fl, BW, and change body composition and/or if tolerance develops. The i.p. studies will establish whether ph-SAT may be useful in a clinical setting. Next, using computer operated feeding modules, control rats will be pair fed (PF) to ph-SAT treated animals to study efficiency of food utilization. These above studies will also determine whether PF control rats will overeat when returned to ad lib feeding, whether long-term PF controls will lose BW similarly to ph-SAT treated rats, and whether ph-SAT treated rats do not lower their metabolic rate similar to PF rats. Next, it will be determined whether any of the BW lost following treatment with ph-SAT is due to fluid loss or to changes in activity (running wheels). Next antibodies to ph-SAT and purified rat SAT will be raised in rabbits for the initial development of an ELISA, so in the future it can be ascertained whether blood SAT varies in a manner consistent with it having a role in the control of ingestion and BW. The antibodies will also be given to rats i.v., using Alzet pumps, to determine if their Fl and BW can in increased; if this occurs it would be of interest in the treatment of pathological anorexias and in the livestock industry. In total, the above studies will help establish SAT's role in the control of Fl and BW and set the direction of future studies.